This phase II trial is studying how well giving capecitabine together with tipifarnib works in treating women with taxane-resistant metastatic breast cancer. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Giving capecitabine together with tipifarnib may kill more tumor cells

Objective response rate (PR+CR) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Progression-free survival (PFS) [ Time Frame: From registration to progression or to death from any cause without documentation of progression, assessed up to 5 years ] [ Designated as safety issue: No ]

The Kaplan-Meier method will be used to estimate distributions.

Time to treatment failure (TTF) [ Time Frame: From registration to disease progression, permanent discontinuation of treatment due to toxicity, or death, whichever occurs first, assessed up to 5 years ] [ Designated as safety issue: No ]

The Kaplan-Meier method will be used to estimate distributions.

Overall survival (OS) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

The Kaplan-Meier method will be used to estimate distributions.

Incidence of toxicities [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Patients are followed every 3 months for 2 years and then every 6 months for 1 year.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Female

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Female patients with histologically confirmed adenocarcinoma of the breast with manifestations of metastatic progression

Patients must have at least one objective measurable disease parameter as defined by RECIST criteria; tumor measurements and evaluation of non-measurable sites must be performed within 4 weeks prior to registration

ECOG performance status 0-2

In order to be eligible for inclusion, patients must meet all of the following criteria with regard to prior cytotoxic therapy: (1) prior treatment with an anthracycline (e.g., doxorubicin, epirubicin) either in the adjuvant/neoadjuvant setting and/or for metastatic disease, (2) prior treatment with a taxane (i.e. paclitaxel, docetaxel) for metastatic disease, or relapse while receiving adjuvant taxane therapy (3) progressive disease while receiving taxane therapy or up to 30 days after receiving the last taxane dose, (4) no more than three prior cytotoxic regimens for metastatic disease, (5) no prior treatment with capecitabine or 5-flourouracil for metastatic disease

Prior hormonal therapy in either the metastatic or adjuvant/neoadjuvant setting is allowed, but patients must have been off such therapy for greater than or equal to 1 week prior to registration

No prior radiotherapy other than to the conserved breast, to the postmastectomy chest wall or to a limited field involving less than 25% of marrow - containing bone

Previously irradiated tumors cannot be used to assess a clinical response; patients will not be eligible for this study if the previously irradiated tumors constitute the only site of measurable disease

Patients must not have previously received tipifarnib or other farnesyl transferase inhibitors

Patients must be disease-free of prior malignancies for > 5 years with the exception of curatively treated basal or squamous cell carcinomas of the skin or carcinoma in situ of the cervix

Patients must not be pregnant or breastfeeding since there is no information regarding the use of these agents in this population; a negative serum or urine pregnancy test is required within 14 days prior to registration if pre- or perimenopausal (i.e., last menstrual period within one year of registration)

Women of childbearing potential are strongly advised to use an accepted and effective method of contraception

Patients with current or previously treated brain metastases are ineligible; patients who are taking enzyme inducing anticonvulsant medications are also not eligible (e.g., phenobarbital, phenytoin)

Patients must not have had prior organ allograft or received immunosuppressive therapy

Patients must not have any uncontrolled intercurrent illness including, but not limited to, chronic nausea/vomiting, complete or partial bowel obstruction, dysphagia/odynophagia with inability to swallow pills, ongoing or active infection, symptomatic cardiovascular disease, or other chronic medical or psychiatric conditions that would impair compliance or would substantially increase the risk of participating in this study

Patients must not have received previous treatment with cytotoxic drugs, and/or radiotherapy < 4 weeks prior to registration; concurrent radiation therapy is not permitted

Because of the potential for a drug interaction between warfarin and both tipifarnib and capecitabine, patients taking warfarin adjusted to an elevated INR are not eligible; patients taking prophylactic low-dose warfarin (i.e., 1 mg daily) are eligible, but a PT and INR are required within 2 weeks of registration and must be normal

Patients with CTC v 3.0 grade 2-4 neuropathy are not eligible

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00077363